Clinical Characteristics of Idiopathic Granulomatous Mastitis in a Hispanic Border Population: A Case Series and Literature Review

Idiopathic granulomatous mastitis (IGM) is an autoimmune condition of the breast that is commonly encountered in women of non-white ethnicity such as Southeast Asians, Middle Easterners, and Hispanics. This condition often presents as a painful breast mass, and many patients undergo invasive diagnostic procedures or surgical excision, which can lead to disfiguring scars. Early recognition and prompt treatment with immunosuppressive medications can prevent invasive workups and management. Although previously thought to require an exclusively surgical approach, it now prompts interdisciplinary management. In this context, we present a case series of patients with IGM in a Hispanic population of South Texas.


Introduction
Idiopathic granulomatous mastitis (IGM) is an inflammatory condition of the breast that has historically posed diagnostic challenges and is associated with a lack of consensus regarding management strategies.While various autoimmune diseases can occasionally target the breast, IGM is an autoimmune condition specific to the breast [1].There is 12 times more predominance in women of Hispanic, Middle-Eastern, and Southeast Asian origin [2].
The clinical presentation of IGM varies among patients and can range from a mass that grows over time to unilateral painful mass, skin induration, skin ulceration, and areolar retraction to fistula formation [10].Imaging tests, such as ultrasonography, MRI, or mammography, may reveal non-specific features in most cases, leading to biopsy.Histopathology may reveal non-necrotizing granulomas and organized microabscesses with multi-nucleated giant cells, lymphocytes, plasma cells, and epitheloid histiocytes [11].
The current knowledge of IGM as being an inflammatory, auto-immune disease has diverted the patient's care from surgical to medical treatment, specifically seeking rheumatological care.With this case series, we hope to provide insight into the clinical presentations of IGM and propose non-invasive management of IGM through a multispecialty approach.

Method
We conducted a retrospective case series at an outpatient Rheumatology department between May 2022 and May 2023.The study identified five patients who were diagnosed with granulomatous mastitis.We analyzed their clinical presentation, demographic data, pathology findings, and management modalities upon chart review.All patients were referred to Rheumatology by a breast surgeon after undergoing a biopsy for breast mass evaluation.Patients were separated based on the treatment modality used and clinical outcome.
The clinical characteristics of the IGM/breast mass determined treatment modalities.These included antibiotic + COX-2 inhibitor, methotrexate (MTX) alone, MTX plus steroid therapy, or high-dose steroid only.Patients were followed for an average of six months.Complete remission was considered with

Results
All of the patients received initial treatment with antibiotics, mainly doxycycline.In addition to antibiotics, celecoxib was given to 80% (Cases 1, 2, 4, 5) of the patients for a minimum of three weeks.Among these patients, 60% (Cases 2, 4, 5) had a relapse after three weeks and required repeat treatment with antibiotics and additional treatment.Twenty percent (20%) (Case 3) received only corticosteroids.Twenty percent (20%) (Case 1) of the patients achieved full remission of the disease.
Four out of five patients were treated with prednisone starting at a dose of 20 mg and tapered down to 10 mg for an average of five months.All four patients experienced remission within an average of three months.Of the patients who received prednisone, 25% experienced relapse after discontinuation.An additional agent, methotrexate 10 mg Q weekly, was given to 25% of the patients.
Two of the five patients had incision and drainage (I&D) of the mass before any treatment was initiated.
One patient had an I&D after treatment was started.
Out of the five patients studied, one was a 30-week pregnant woman (Case 3), one was an 80-year-old healthy female (Case 1), and the other three were between the ages of 24 and 32.Overall, only two out of five (⅖) patients experienced complete resolution at six months from all treatments.One out of five (⅕) continued to have a persistent condition and two out of five (⅖) required prolonged treatment/addition of immunosuppressive agents to achieve remission.

Discussion
We conducted a literature review, to identify articles on granulomatous mastitis and therapeutic approaches, we did a PubMed search using the Mesh terms "Granulomatous Mastitis/drug therapy" OR "Granulomatous Mastitis/surgery" OR "Granulomatous Mastitis/therapy".A total of 224 articles were found.We included all full-length case series and retrospective and cohort studies but excluded studies describing patients with granulomatous mastitis due to tuberculosis or other infectious causes, papers not published in English, papers that focused on invasive procedures, and descriptive papers with no intervention or outcome.Ten papers were included in the final analysis.
Many autoimmune diseases may affect breast tissue [12], including IGM, which is a specific autoimmune disease that primarily affects young women of childbearing age.However, our case series has shown evidence of IGM in an elderly female as well.IGM can often present symptoms similar to breast cancer, which is why patients undergo invasive procedures to receive a prompt diagnosis and treatment.Two of our patients also had other extramammary manifestations, such as erythema nodosum and alopecia, therefore all patients diagnosed with IGM should also be tested to rule out other underlying autoimmune diseases and infectious diseases, such as tuberculosis.
In terms of initial diagnostic testing, patients typically undergo radiological studies such as breast ultrasound and mammography [13].A BI-RADS 2 or 3 diagnosis does not always require invasive procedures like surgical resection.However, most patients undergo confirmatory core-needle biopsies.Histologically, the results are consistent across all cases, with predominantly inflammatory granulomatous changes and negative cultures.
Clinicians have been perplexed by the chronic nature and unclear cause of IGM, making their management a complex task.This discussion focused on the challenges faced in diagnosing such a disease, the lack of standardized treatments available, and potential avenues for future research.Current literature reveals a wide range of treatment responses, leading to significant heterogeneity.
Our case series included only Hispanic patients, confirming that this is a common entity in this patient population [12].
There is no standardized treatment protocol for IGM, various modalities have been used such as antibiotics, surgical excision, and immunosuppressive therapy with methotrexate, celecoxib, and corticosteroid.However, prednisone has been shown to achieve the longest remission periods in 69% of the cases followed by surgery in 65 % [14].

Conclusions
There is scope for further research to understand the underlying mechanisms that trigger inflammatory responses leading to IGM.It is also important to investigate risk factors, such as environmental, genetic, and immune-mediated, to categorize and personalize management strategies.Additionally, a large-scale multidisciplinary collaboration to create a comprehensive registry could help in understanding the epidemiology of the disease in the future.

FIGURE 4 :
FIGURE 4: Photomicrograph of left breast core biopsyHematoxylin and eosin staining original magnification x20, highlighting acute and chronic inflammatory cells including lymphocytes, epitheloid histiocytes, spindle cells, plasma cells, and fat cells surrounded by inflammation.

TABLE 1 : Case reports
BI-RADS: Breast Imaging-Reporting and Data System